We have previously shown that nutritional and metabolic factors can rapidly alter the synthesis and release of a brain neurotransmitter, serotonin, by providing the brain with more or less of serotonin's amino acid precursor, tryptophan. This effect a) is mediated by changes in plasma levels of tryptophan and of other neutral amino acids that compete with tryptophan for uptake into the CNS; b) is associated with changes in some brain functions thought to involve serotoninergic neurons: c) can be reproduced by giving pure amino acid mixes; and, d) apparently also occurs in humans. Similar observations made subsequently at M.I.T. on choline/acetylcholine and tyrosine/catecholamines have enabled us to propose general criteria for establishing precursor control of a neurotransmitter's synthesis, and to expand uses of nutrient-precursors for treating various human disorders. Proposed studies are designed to: 1) continue examining the uses of tryptophan (alone or in amino acid mixes) in affecting appetite, blood pressure, and brain composition; 2) characterize fully the effects on rats and humans of tyrosine administration (e.g., on central and peripheral catecholamine synthesis and release; on blood pressure; on prolactin secretion; on sensitivity to environmental stimuli; in Parkinson's Disease and depression); 3) expand preliminary observations on nutritional and precursor control of the synthesis of glycine (and possibly other non-essential amino acid transmitters); 4) Examine changes in the nutritional control of brain composition occurring in diabetes; and 5) characterize food- and time-induced variations in plasma and brain levels of basic and acidic amino acids. we will also develop new micromethods for assaying some of these compounds in body fluids and tissues.